Michael C. Stallings - US grants

DESCRIPTION (Adapted from the Applicant's Abstract): The purpose of this research is to investigate the extent to which the relative contributions of genetic and levels of hierarchically organized traits show more change than others. Personality data from three major assessment instruments (Eysenck's Personality Questionnaire, Cloninger's Tridimensional Personality Questionnaire, and the Karolinska Scales of Personality-to approximate J. Gray's model) provide the basis for multivariate investigations of personality structure in adulthood. -- response to NIH PA-98-076 (Behavior Genetics in Adulthood and Old Age), we propose secondary analyses of this unique item pool obtained on a large sample (N = 4119 individuals) of older adult twins 50 to 96 years of age. Our investigations will: 1) examine the phenotypic factor structure of the different personality dimensions within and across these three models of personality; 2) use biometrical analysis of twin data to estimate the genetic and environmental sources of variance in the primary facets/subscales and higher-order personality dimenions; 3) assess the factor invariance and/or changes in the genetic and environmental architecture of comparable personality factors across age-cohorts; 4) evaluate the joint factor structure underlying the three personality models through biometrical analysis of the combined facet and item-level data pool; 5) apply quantitative genetic methods to optimize factor structure for maximal genetic and environmental sources of variance; and 6) evaluate the external (i.e., predictive) validity of the existing and derived personality scales. The overarching goal of our multivariate investigations is to improve the measurement of personality concepts for gerontologically-relevant research.

DESCRIPTION (provided by applicant): We request funds to continue a prospective, longitudinal, adoption study of transitions to adulthood. The proposed research aims to increase knowledge about the important familial determinants of children's social and economic well being as they make the transition from adolescence into young adulthood. Specific hypotheses address individual and familial influences on educational attainment, occupational attainment, and family-formation choices, and how the quality of early family relationships shapes adult parent-child relationships. We address these questions in the context of a longitudinal adoption design, which offers an opportunity to carry out powerful tests of socialization and social-psychological theories. The adoption design allows us to test familial determinants of adult outcomes independently of genetic effects. Further, we capitalize on the resources of the Colorado Adoption Project (CAP), a long-term, longitudinal adoption study of 245 adoptive families and 245 nonadoptive families. The CAP children, their siblings, and their home environments have been assessed repeatedly since infancy using a broad, multivariate battery of social, environmental, and behavioral measures. We propose to continue longitudinal assessment of the CAP probands, their siblings, and their parents, as the CAP children continue to make the transition into young adulthood (reach age 25-30). The proposed research is innovative, both in the field of behavioral genetics and the field of social demography, in that it brings behavioral genetic methods to bear on social demographic phenomena and on the study of life-course developmental processes. This study promises to advance our understanding of how family factors influence adult outcomes, and to enrich socialization theories and models of life-course development.

DESCRIPTION (provided by applicant): There are substantial genetic contributions to the development of complex behaviors in humans and animals. The research challenge is to understand how these genetic contributions influence the developmental pathways that lead to complex behaviors of relevance to human health and disease. Developmental behavior genetics integrates the perspectives of quantitative genetics, molecular genetics, neurobiology and, increasingly, the resources of bioinformatics, into the study of behavioral development. Using multidisciplinary approaches, the genetic contributions to normal and abnormal development can be investigated. The application of biometrical genetic techniques and the development of quantitative trait loci methods allows the mapping of genes that regulate complex polygenic traits, as well as the development of quantitative information about stability and change during development and the causes of specificity and generality, or comorbidity, across behavioral phenotypes. Information from such analyses, along with neurochemical neuropharmacological, and molecular genetic studies, will provide an understanding of how gene function is related to behavioral development. The Institute for Behavioral Genetics (IBG) at the University of Colorado has actively pursued the goals of behavior genetics for nearly four decades. Its faculty is distinguished and active in research. Major research projects are now in progress in both human and animal behavior genetics. Facilities are available for gene mapping studies in human, mouse and nematode models, behavioral and biochemical studies in mice and nematodes, and biometrical analyses of extensive human phenotypic twin, family, adoption, and clinical datasets that can be cross-linked to DNA data. Funds are requested to support 5 predoctoral and 2 postdoctoral trainees. Predoctoral trainees receive doctorate degrees from a cooperating academic unit and certification in behavior genetics. Academic requirements in the training program include training in behavior genetics, quantitative and biometrical genetics, theoretical and computer-based statistics, molecular genetics, bioinformatics, responsible conduct of research, and courses on behavioral and clinical phenotypes. Additional requirements vary according to the degree granting academic unit. Research experience is an integral part of training. Postdoctoral trainees also pursue a formalized program that emphasizes individual research as well as competence in molecular and quantitative behavior genetics. Other activities in their preparation include: supervision of students and/or technicians, hosting of seminar speakers, guest lecturing, and mandatory attendance in a course on the responsible conduct of research and a weekly journal club.

DESCRIPTION (provided by applicant): This RO1 application seeks five years of support to conduct a molecular genetics study of an existing community-based sample of over 2,400 participants including 500 cohort members (G2 targets), their close- aged siblings, their parents (G1), their romantic partners, and their oldest biological child (G3). The broad objective of this proposal is to evaluate genetic (G), environmental (E), and gene x environment interaction (GxE) effects on a set of core personality attributes that are linked to a host of important developmental outcomes using a weighted, family-based genome-wide association study (GWAS). Specifically, we propose to examine genetic and environmental contributions to the latent traits of Behavioral Disinhibition (BD) and Dispositional Resilience (DR). BD reflects excessive pursuit of exciting appetitive stimuli, disregard for the aversive consequences of risky behaviors, and a tendency to engage in aggressive acts that demonstrate a lack of concern for others. Conversely, DR reflects emotional stability, interpersonal sensitivity, and a self-confident and self-directed orientation to meeting achievement-related challenges. These attributes are present as early as toddlerhood and continue to have important developmental consequences across the life course. In particular these attributes influence whether individuals develop specific competencies and strong interpersonal relationships or whether individuals develop problems that can significantly impair their health and well-being such as involvement with substances, crime, and engaging in risky behaviors. To address these important questions, we will use both existing data from the Family Transitions Project (FTP) as well as genetic information to be collected as part of the proposed study. The FTP was initiated in 1989 when the G2 targets were early adolescents and has continued with annual assessments since that time. The G2 cohort members now average 33 years of age. Each generation in the study has been assessed over a several year period of time using a measurement strategy that is both extensive (i.e., covers multiple domains of personal and social characteristics) and intensive (i.e., employs a multi- informant approach that includes self-reports, other family member reports, teacher reports, ratings by trained observers, school records and public records). Requested funds will be used to collect DNA and genotype the FTP participants. Genotypic information will be combined with the existing archive of contextual and phenotypic data to evaluate genetic and environmental influences on BD and DR. In particular, the unique family structures in this sample include genetically-informative parent-offspring (both G1-G2 and G2-G3) and sibling relationships (G2) which will be ideal for Family-Based Association Test (FBAT) methods. PUBLIC HEALTH RELEVANCE: The goal of the current study is to increase understanding of genetic and environmental factors that shape specific personal attributes that are linked with both maladaptive and adaptive developmental outcomes across the life span. Attributes such as achievement motivation, interpersonal sensitivity, and a positive identity tend to promote successful adaptation, whereas attributes linked with behavioral disinhibition are associated with substance use, crime, health risks, and interpersonal difficulties. The clarification of the genetic and environmental underpinnings of these traits has the potential for enormous public health benefits. Indeed, results from the proposed study should provide specific insights that can inform prevention and treatment efforts designed to promote healthy human development and to reduce psychopathology and problem behaviors.

DESCRIPTION (provided by applicant): This Institutional training grant is for training in the field of behavior genetics. The goals of behavior genetics are to elucidate the genetic and environmental components that regulate the development of individual differences in normal and abnormal behavior. Using multidisciplinary approaches, the genetic basis of human development and susceptibility to psychopathology and disease, can be investigated. The application of biometrical, statistical, and quantitative genetic techniques and the development of quantitative trait loci methods allow the mapping and identification of genes that regulate complex traits. Information from such analyses, along with neurochemical, neuropharmacologlcal, neurophysiologlcal, and molecular genetic studies, will provide an understanding of gene function related to health and behavior. The Institute for Behavioral Genetics (IBG) at the University of Colorado has actively pursued the goals of behavior genetics for over 40 years. Its faculty is distinguished and active in research. Major research projects are now in progress in both human and animal behavior genetics, including large scale national collaborative studies amassing DNA repositories and rich phenotypic data sets for studies of behavioral development and mental health. Facilities are available for genotype assay, including genome-wide assays, gene function and expression studies, and behavioral, biochemical, and neurophysiologlcal studies. Funds are requested to support 5 predoctoral and 1 postdoctoral trainee over a total period of 5 years. Predoctoral trainees receive doctorate degrees from a cooperating academic unit and certification in behavior genetics. Academic requirements in the training program include training in behavior genetics, quantitative and biometrical genetics, theoretical and computer-based statistics, molecular genetics, bioinformatics and genomics, responsible conduct of research, and courses on behavioral and clinical phenotypes. Additional requirements vary according to the degree granting academic unit. Research experience is an integral part of training. Postdoctoral trainees also pursue a formalized program that emphasizes individual research as well as competence in molecular and quantitative behavior genetics. Other activities In preparation for research careers in biobehavioral development Include: supervision of students and/or technicians, hosting of seminar speakers, guest lecturing, a weekly journal club, and mandatory attendance In a course on the responsible conduct of research. PUBLIC HEALTH RELEVANCE: This proposal is to train scientists who will be able to contribute significantly to our understanding of genetic contributions to human development and health. A better understanding of human developmental processes and susceptibility to developmental disorders and disease will contribute to the development and application of primary prevention and early intervention techniques to improve health and optimal development.

DESCRIPTION (provided by applicant): The research proposed in this application aims to understand genetic and environmental factors that promote desistance or continuation of problematic substance use and associated high-risk behaviors that began in adolescence. We propose an ~12-year follow-up (6 years after an initial 6-year follow-up) of an extremely affected adolescent sample as they transition into adulthood; this is a critical developmental period when we expect a portion of these individuals to decrease or desist problematic substance use and associated high-risk behaviors, while others will persist with the most serious, destructive behaviors leading to devastatingly high rates of morbidity and mortality. Our central goal is to understand the genetic and environmental factors that delineate these life trajectories. Results from our longitudinal research demonstrate that adolescent-onset substance users, who primarily exhibited abuse of and dependence on marijuana, nicotine, and alcohol during adolescence, progressed in the severity of their substance use five years later. As young adults, they report dramatically high rates of lifetime cocaine (29.2%), amphetamine (29.2%), and opiate (10.8%) use disorders as well as HIV/AIDS-related risk behaviors such as injection drug use (11%) and risky sexual behaviors. Indeed, when compared with community samples, these individuals report more than twice the number of lifetime sexual partners and a 33% higher rate of unprotected sex. Furthermore, they exhibit alarming rates of adult incarceration (55%) and early death (2.6%). This proposal extends our multiple-PI collaboration focused on the genetic epidemiology of adolescent-onset drug dependence. The three specific aims are to: 1) Identify distinct developmental trajectories of substance use, antisocial, and HIV risk behaviors in probands and siblings from adolescence to adulthood. a) Test initial characteristics of the adolescents, such as sex, severity of early onset substance use disorders (SUDs) and conduct disorder (CD), and neurocognitive functioning (e.g., disinhibition) that predict these trajectories and b) Test whether adult resources such as treatment for SUDs, housing stability, occupational stability, and social support are associated with these trajectories. 2) Determine the genetic and environmental architecture of developmental trajectories of substance use disorders, antisocial and HIV risk behaviors. a) Test the moderating role of social context, such as SES, criminal justice involvement, substance abuse treatment/self-help involvement, and stressful life events, in altering genetic influence and b) Test whether moderating effects vary across developmental periods (adolescence, young adulthood, and adulthood). 3) Test the influence of shared versus specific etiologic influences on measures of SUDs, antisocial behaviors, and HIV risk behaviors across development.